THE INFLUENCE OF A SERINE-PROTEASE INHIBITOR, NAFAMOSTAT MESILATE, ONPLASMA COAGULATION, AND PLATELET ACTIVATION DURING EXPERIMENTAL EXTRACORPOREAL LIFE-SUPPORT (ECLS)

Introduction: During extracorporeal circulation the contact between bl ood and the artificial surface of the circuit induces several changes in the hemostatic system. The objective of the present study was to as sess the effect of a serine protease inhibitor - Nafamostat mesilate ( FUT-175) - on coagulation and on platelets during experimental extraco rporeal circulation. Methods: Two identical Extra Corporeal Life Suppo rt (ECLS) circuits were primed with fresh. heparinized human blood and circulated for 24 h. FUT-175 was added to one of the paired circuits and the other was used as a control. The following FUT-175 concentrati ons were employed: (1) 7.1 mg/l/h, (2) 14.2 mg/l/h, (3) 14.2 mg/l/h 85.5 mg given as an initial bolus, (4) 28.5 mg/l/h + 171 mg given as a n initial bolus. Blood samples were collected from the circuits before the start of the perfusion and at 0.5, 1, 3, 12, and 24 h of perfusio n,and analysed for platelet count, plasma betathromboglobulin (beta-TG ), platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa expression, t hrombin/antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2 ), fibrinogen, D-dimer, and plasminogen activator inhibitor 1 activity (PAI-1). Results: Significantly higher platelet membrane GPIb express ion and lower plasma beta-thromboglobulin levels were observed in the circuits holding FUT-175, suggesting a lower degree of platelet activa tion. Also, a reduced activation of the coagulation system was observe d in the ''FUT-circuits'', as reflected by the levels of F1+2 and TAT, and the PAI-1 activity that was rapidly inactivated. Conclusion: FUT- 175 reduces the activation of platelets and plasma coagulation in an i n vitro ECLS model.